#1270 Exploring the shift in gut microbiota due to renal ischemia/reperfusion injury in rats

Abstract Background and Aims Acute kidney injury (AKI) due to renal ischemia/reperfusion (I/R) is a major clinical problem in renal transplantation and partial nephrectomy, which is associated with morbidity and mortality and substantial healthcare expenditures, but there is no effective and specific treatment. Recently, the clinical impact of the interaction between gut bacteria and the kidney function has become increasingly clear. Experimental evidence has highlighted a bidirectional relationship between gut microbiota and kidney disease. Therefore, we investigated the possibility that I/R can ameliorate AKI by studying gut-renal interactions and gut microbiota in AKI. Method We induced varying degrees of renal I/R injury in adult male Wistar rats by clamping the left renal pelvis for 30 and 45 minutes, simulating mild and severe conditions, respectively. These samples were subjected to extensive histologic examination using standard techniques such as hematoxylin and eosin (HE), Sirius Red, and F4/80 staining. In addition, we performed a quantitative analysis of the mRNA expression levels of fibrotic and inflammatory markers in both kidney and colon tissues using real-time PCR. Gut microbiota genomic DNA was extracted from rat feces and microbial 16S ribosomal RNA (rRNA) gene sequencing was performed. Results Renal function deteriorated with increasing ischemia time and fibrosis progressed, as confirmed by Sirius Red staining and qPCR of fibrosis genes such as TGFB. The expression of inflammatory genes such as IL-1B and IL-6 was also increased. The expression of inflammatory genes such as Toll-like receptor, C3, and IL-1B in the intestine also increased with ischemia time. In the fecal microbiota, the total read percentage of Bacteroides acidifaciens at the species level increased with increasing ischemia time. Conclusion The observed shifts in gut microbiota composition may serve as a critical indicator of chronic kidney disease (CKD)-induced gut dysbiosis secondary to AKI. This finding highlights the need for further research into the identification and migration patterns of the gut microbiota, which represents a promising avenue for early detection, prevention, and therapeutic intervention in AKI. Future investigations elucidating the mechanisms by which the microbiota influence IRI-induced AKI and the development of practical therapeutic strategies have the potential to significantly improve clinical outcomes in patients suffering from IRI-induced AKI.